Occludin is involved in adhesion, apoptosis, differentiation and Ca2+-homeostasis of human keratinocytes: implications for tumorigenesis.

Tight junction (TJ) proteins are involved in a number of cellular functions, including paracellular barrier formation, cell polarization, differentiation, and proliferation. Altered expression of TJ proteins was reported in various epithelial tumors. Here, we used tissue samples of human cutaneous s...

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Autores principales:	Susanne Rachow, Michaela Zorn-Kruppa, Ulrich Ohnemus, Nina Kirschner, Sabine Vidal-y-Sy, Peter von den Driesch, Christian Börnchen, Jürgen Eberle, Michael Mildner, Eik Vettorazzi, Rita Rosenthal, Ingrid Moll, Johanna M Brandner
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7d682f6261924742910e67a9613ceb94
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spelling	oai:doaj.org-article:7d682f6261924742910e67a9613ceb942021-11-18T07:58:55ZOccludin is involved in adhesion, apoptosis, differentiation and Ca2+-homeostasis of human keratinocytes: implications for tumorigenesis.1932-620310.1371/journal.pone.0055116https://doaj.org/article/7d682f6261924742910e67a9613ceb942013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23390516/?tool=EBIhttps://doaj.org/toc/1932-6203Tight junction (TJ) proteins are involved in a number of cellular functions, including paracellular barrier formation, cell polarization, differentiation, and proliferation. Altered expression of TJ proteins was reported in various epithelial tumors. Here, we used tissue samples of human cutaneous squamous cell carcinoma (SCC), its precursor tumors, as well as sun-exposed and non-sun-exposed skin as a model system to investigate TJ protein alteration at various stages of tumorigenesis. We identified that a broader localization of zonula occludens protein (ZO)-1 and claudin-4 (Cldn-4) as well as downregulation of Cldn-1 in deeper epidermal layers is a frequent event in all the tumor entities as well as in sun-exposed skin, suggesting that these changes result from chronic UV irradiation. In contrast, SCC could be distinguished from the precursor tumors and sun-exposed skin by a frequent complete loss of occludin (Ocln). To elucidate the impact of down-regulation of Ocln, we performed Ocln siRNA experiments in human keratinocytes and uncovered that Ocln downregulation results in decreased epithelial cell-cell adhesion and reduced susceptibility to apoptosis induction by UVB or TNF-related apoptosis-inducing ligand (TRAIL), cellular characteristics for tumorigenesis. Furthermore, an influence on epidermal differentiation was observed, while there was no change of E-cadherin and vimentin, markers for epithelial-mesenchymal transition. Ocln knock-down altered Ca(2+)-homeostasis which may contribute to alterations of cell-cell adhesion and differentiation. As downregulation of Ocln is also seen in SCC derived from other tissues, as well as in other carcinomas, we suggest this as a common principle in tumor pathogenesis, which may be used as a target for therapeutic intervention.Susanne RachowMichaela Zorn-KruppaUlrich OhnemusNina KirschnerSabine Vidal-y-SyPeter von den DrieschChristian BörnchenJürgen EberleMichael MildnerEik VettorazziRita RosenthalIngrid MollJohanna M BrandnerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e55116 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Susanne Rachow Michaela Zorn-Kruppa Ulrich Ohnemus Nina Kirschner Sabine Vidal-y-Sy Peter von den Driesch Christian Börnchen Jürgen Eberle Michael Mildner Eik Vettorazzi Rita Rosenthal Ingrid Moll Johanna M Brandner Occludin is involved in adhesion, apoptosis, differentiation and Ca2+-homeostasis of human keratinocytes: implications for tumorigenesis.
description	Tight junction (TJ) proteins are involved in a number of cellular functions, including paracellular barrier formation, cell polarization, differentiation, and proliferation. Altered expression of TJ proteins was reported in various epithelial tumors. Here, we used tissue samples of human cutaneous squamous cell carcinoma (SCC), its precursor tumors, as well as sun-exposed and non-sun-exposed skin as a model system to investigate TJ protein alteration at various stages of tumorigenesis. We identified that a broader localization of zonula occludens protein (ZO)-1 and claudin-4 (Cldn-4) as well as downregulation of Cldn-1 in deeper epidermal layers is a frequent event in all the tumor entities as well as in sun-exposed skin, suggesting that these changes result from chronic UV irradiation. In contrast, SCC could be distinguished from the precursor tumors and sun-exposed skin by a frequent complete loss of occludin (Ocln). To elucidate the impact of down-regulation of Ocln, we performed Ocln siRNA experiments in human keratinocytes and uncovered that Ocln downregulation results in decreased epithelial cell-cell adhesion and reduced susceptibility to apoptosis induction by UVB or TNF-related apoptosis-inducing ligand (TRAIL), cellular characteristics for tumorigenesis. Furthermore, an influence on epidermal differentiation was observed, while there was no change of E-cadherin and vimentin, markers for epithelial-mesenchymal transition. Ocln knock-down altered Ca(2+)-homeostasis which may contribute to alterations of cell-cell adhesion and differentiation. As downregulation of Ocln is also seen in SCC derived from other tissues, as well as in other carcinomas, we suggest this as a common principle in tumor pathogenesis, which may be used as a target for therapeutic intervention.
format	article
author	Susanne Rachow Michaela Zorn-Kruppa Ulrich Ohnemus Nina Kirschner Sabine Vidal-y-Sy Peter von den Driesch Christian Börnchen Jürgen Eberle Michael Mildner Eik Vettorazzi Rita Rosenthal Ingrid Moll Johanna M Brandner
author_facet	Susanne Rachow Michaela Zorn-Kruppa Ulrich Ohnemus Nina Kirschner Sabine Vidal-y-Sy Peter von den Driesch Christian Börnchen Jürgen Eberle Michael Mildner Eik Vettorazzi Rita Rosenthal Ingrid Moll Johanna M Brandner
author_sort	Susanne Rachow
title	Occludin is involved in adhesion, apoptosis, differentiation and Ca2+-homeostasis of human keratinocytes: implications for tumorigenesis.
title_short	Occludin is involved in adhesion, apoptosis, differentiation and Ca2+-homeostasis of human keratinocytes: implications for tumorigenesis.
title_full	Occludin is involved in adhesion, apoptosis, differentiation and Ca2+-homeostasis of human keratinocytes: implications for tumorigenesis.
title_fullStr	Occludin is involved in adhesion, apoptosis, differentiation and Ca2+-homeostasis of human keratinocytes: implications for tumorigenesis.
title_full_unstemmed	Occludin is involved in adhesion, apoptosis, differentiation and Ca2+-homeostasis of human keratinocytes: implications for tumorigenesis.
title_sort	occludin is involved in adhesion, apoptosis, differentiation and ca2+-homeostasis of human keratinocytes: implications for tumorigenesis.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/7d682f6261924742910e67a9613ceb94
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Occludin is involved in adhesion, apoptosis, differentiation and Ca2+-homeostasis of human keratinocytes: implications for tumorigenesis.

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